Department of Human Anatomy, Zunyi Medical University, Zunyi, Guizhou, China.
Key Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine Center, Affiliated Hospital of Zunyi Medical University, 149 Dalian Rd., Zunyi, 563000, Guizhou, China.
J Mol Neurosci. 2019 Oct;69(2):324-332. doi: 10.1007/s12031-019-01361-5. Epub 2019 Jul 20.
Transforming growth factor-β (TGF-β) is a key factor that promotes fibrosis or scar formation, which could become an obstacle in the repair of impaired axons in the central nervous system (CNS) of the human body resulting from diseases or injuries. Considering that major pathological reactions occur during this process, we focused on TGF-secreting M2 macrophages to identify the interactions between M2 macrophages and astrocytes (AS) and verify the specific mechanism of fibrosis or glial scar formation. In the present study, we used the Transwell coculturing technique and found an increase in glial fibrillary acidic protein (GFAP), neurocan, IL-13, and TGF-β expression after incubation for 48 h; the expression of these proteins decreased when additional inhibitors of the TGF-β receptor were added. We concluded that fibrosis or glial scar formation would be enhanced by the secretion of neurocan from AS, resulting from the release of TGF-β from M2 macrophages. We also used M2 macrophage-conditioned medium to further confirm this finding in a subsequent experiment. We hope that the findings in this research could provide a foundation for locating new targets for treating CNS diseases or injuries.
转化生长因子-β（TGF-β）是促进纤维化或瘢痕形成的关键因素，这可能成为人体中枢神经系统（CNS）中因疾病或损伤而受损轴突修复的障碍。鉴于在此过程中会发生主要的病理反应，我们专注于分泌 TGF-β的 M2 巨噬细胞，以确定 M2 巨噬细胞和星形胶质细胞（AS）之间的相互作用，并验证纤维化或神经胶质瘢痕形成的具体机制。在本研究中，我们使用 Transwell 共培养技术，发现孵育 48 小时后 AS 中 GFAP、神经粘蛋白、IL-13 和 TGF-β 的表达增加；当添加 TGF-β 受体的额外抑制剂时，这些蛋白质的表达减少。我们得出结论，AS 中神经粘蛋白的分泌会增强纤维化或神经胶质瘢痕形成，这是由 M2 巨噬细胞释放 TGF-β 引起的。我们还使用 M2 巨噬细胞条件培养基在随后的实验中进一步证实了这一发现。我们希望本研究的结果能为寻找治疗 CNS 疾病或损伤的新靶点提供基础。
